This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent studies in mice have shown that eliminating dietary leucine in combination with caloric restriction results in rapid loss of visceral fat stores within seventeen days, without negative health effects. The reduction in visceral fat is correlated with reduced hepatic fat synthesis and serum insulin levels. Thus elimination of dietary leucine mimics a fasting response despite the presence of normal levels of fat and carbohydrates in the test diet. Based upon metabolic similarities between rodent and humans, we hypothesize that a low leucine (LowLEU) diet will stimulate a rapid loss of adipose stores in humans. We propose to conduct a human dietary experiment to test this hypothesis. The goal of this research is develop a novel, safe, and efficacious dietary regime for the rapid loss of excess fat stores. The specific aims of the study will be to: 1) determine if a low leucine diet in combination with moderate caloric restriction will result in rapid loss of excess adipose stores in overweight (BMI= 25-30) individuals;2) determine if a low leucine diet is tolerated by test subjects;and 3) determine if a low leucine diet is safe as a short-term diet. The proposed LowLEU diet experiment will be conducted over 14 days and will entail 48 test subjects half of which will be administered the LowLEU diet (7% RDA) and half administered the identical diet but with normal leucine levels. Body composition and metabolic parameters will be assessed before and after the 14 day treatment period. We expect to see a rapid reduction in adipose stores as revealed by DXA body composition and BMI analysis. This is a pilot project for which we hope to use for the basis of grant proposal to the NIH to examine the impact of altering dietary essential amino acids in the treatment of obesity and diabetes.